Acute stroke affects over 700,000 people annually in the United States(US).(1) Currently, the only FDA approved treatment for acute ischemic stroke is intravenous recombinant tissue plasminogen activator (rt-PA) administered within three hours of stroke symptom onset.(2) Only 3-8% of all stroke patients in the US are treated with rt-PA because most present to healthcare facilities beyond the three hour treatment window.1 Alternative therapies must be researched to provide treatment options for the hundreds of thousands of stroke patients for which no approved acute therapy exists. Acute antiplatelet loading is utilized in the treatment of cardiac vascular occlusive disease. The use of an animal model to test anti platelet loading as a stroke intervention will provide a rigorous foundation for translation into human clinical trials. The purpose of this study is to: 1) determine the effect of standard aspirin treatment, low anti platelet loading, and high antiplatelet loading on time to platelet aggregation in the rabbit small clot embolic model;2) to determine the efficacy of standard aspirin treatment, low anti platelet loading, and high antiplatelet loading on reduction of infarct volume in the rabbit small clot embolic model (RSCEM);and 3) to compare neurologic behavior outcomes in the standard aspirin treatment, low anti platelet loading, and high anti platelet loading group in the rabbit small clot embolic model. White, New Zealand rabbits will be randomized to standard aspirin treatment, low antiplatelet loading dose, or high antiplatelet loading dose. A clot (embolization) will be introduced into each animal via the RSCEM methodology. Rabbits will receive treatment according to randomization assignment two hours post-embolization. Behavioral outcomes will be assessed at hour 0,5,8,24, and 48 post-embolization via the rabbit clinical rating scale.(54) After hour 48, animals will be sacrificed and hemorrhage rate and infarct volume will be compared. The outcomes of the proposed research project will serve the 700,000 people who suffer acute stroke each year. A gap in the knowledge exists regarding novel treatment of ischemic stroke beyond the thrombolytic window with anti platelet loading. Filling this gap may result in a decrease in stroke burden to the healthcare community and stroke victims and their caregivers. In addition, assessment for maximal antiplatelet dosing that is safe is critical to the treatment of many aspirin and c1opidogrel resistant patients. This animal model research will translate into the support of a new stroke therapy that will limit brain injury, extend healthy life, and reduce disability from ischemic stroke.